The Biphasic Relationship between Regional Brain Senile Plaque and Neurofibrillary Tangle Distributions: Modification by Age, Sex, and APOE Polymorphism
Abstract
Epidemiologic studies indicate that elderly women are at higher risk for Alzheimer disease compared to men. In order to pathologically verify this result, the extent of AD brain lesions (NFT and SP) was compared for men and women at each age, that is, at each decade from 25 years to 95 years, in a large sample of > 5000 routine autopsy cases. Women had more affected brain regions beginning in late middle age. They also had more extensive SP depositions throughout the brain compared to men at each early NFT stage I, II, and III. At later NFT stages IV, V, and VI both men and women had extensive SP deposits. The gender gap in SPs at early NFT stages was large and specific to women who carried the APOE4 allele (P <.001) and in addition to the acceleration in NFT stage also found for APOE4+ women.
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One autopsy study found that women had more senile plaques, and the association was stronger among ε4 carriers.
“One autopsy study found that women had more senile plaques, and the association was stronger among ε4 carriers [17]”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [17]
Two other studies reported differential associations between APOE ε4 and AD pathological indices in women and men, but they did not contain a formal interaction test between sex and APOE ε4.
“Although two other studies reported differential associations between APOE ε4 and AD pathological indices in women and men [17,24], they do not contain any formal interaction test between sex and APOE ε4.”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [17]
The link between Alzheimer's disease and APOE4 is more prominent in women than in men.
“At molecular levels, the link between AD and a genetic risk factor, APOE4 is much more prominent in women than men [7, 8].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [7]
ApoE4 carriers have increased Aβ burden.
“apoE4 carriers have increased A burden (Beffert et al., 1999;Corder et al., 2004;Fryer et al., 2005).”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Corder et al., 2004
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References 9 · Cited by 254
- Authors
- CORDER, E. H., GHEBREMEDHIN, E., TAYLOR, M. G., THAL, D. R., OHM, T. G., & BRAAK, H.
- Affiliations
- Duke University (US)
- Goethe University Frankfurt (DE)
- University of Bonn (DE)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- CORDER, ELIZABETH H.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2004-06
- Volume
- 1019
- Issue
- 1
- Pages
- 24-28
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2135563234
- Cited by
- 254
- References
- 9
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 27 · 2023: 12 · 2022: 11 · 2021: 18 · 2020: 21 · 2019: 18 · 2018: 18 · 2017: 10 · 2016: 23 · 2015: 11 · 2014: 12 · 2013: 6 · 2012: 10
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (T32AG000139)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid plaques, neurofibrillary tangles, sex differences, APOE ε4, APOE polymorphism, brain aging
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Alleles, Apolipoproteins E, Brain, Female, Humans, Male, Middle Aged, Neurons, Polymorphism, Genetic, Sex Factors, Neurofibrillary Tangles, Plaque, Amyloid
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